The present invention relates to carbapenem antibiotics, which are substituted in the 2-position with a carbolinyl derivative.
Thienamycin was an early carbapenem antibacterial agent having a broad spectrum; it has the following formula: ##STR4## Later, N-formimidoyl thienamycin was discovered; it has the formula: ##STR5##
U.S. Pat. Nos. 5,011,832 and 5,025,006 relate to carbapenems of the structure shown below which exhibit antimicrobial activity against,strains of methicillin resistant staphylococci (MRSA). The carbapenems described therein possess a meta-disposed biphenyl moiety attached to the C-2 position of the carbapenem ring. ##STR6##
More recently, U.S. Pat. No. 5,034,384 issued to Greenlee, et al. and EPA 472 306 published on Feb. 26, 1992 addressing compounds of the formula: ##STR7## Such compounds have MRSA and MRCNS activity.
U.S. Pat. No. 5,128,335 issued to DiNinno, et al. on Jul. 7, 1992 addressing compounds of the formula: ##STR8##
U.S. Pat. No. 5,294,610 issued to DiNinno, et al. on Mar. 15, 1994 addressing compounds of the formula: ##STR9##
The carbolinyl carbapenems of the present invention are particularly useful in treating infections caused by gram positive organisms, especially methicillin resistant Staphylococcus aureus (MRSA), methicillin resistant Staphylococcus epidermidis (MRSE), and methicillin resistant coagulase negative Staphylococci (MRCNS). The antibacterial compounds of the present invention thus comprise an important contribution to therapy of these difficult to control pathogens. There is an increasing need for agents effective against such pathogens (MRSA/MRCNS). In addition, certain members of the class have been found to possess a broader spectrum of activity which includes gram negative bacteria.